Epidemiologic studies of worldwide increases in asthma have shown that the prevalence of wheezing varies markedly among countries ranging from 2% in Ecuador to 30% in New Zealand. Differences in allergen exposure and distinct immune responses to the allergens of dust mite and cat may explain some of these epidemiologic findings. It has recently been shown that high exposure to cat allergen compared with dust mite is associated with decreased prevalence of IgE antibody and decreased titers of IgE antibody that are not related to increased total IgE. Furthermore a high proportion of individuals living with a cat have immune tolerance consisting of IgG antibody to cat allergen without IgE antibody. Dramatic decreases in exposure to cat allergen can be associated with increased allergic symptoms upon re-exposure. This project combines three aims to characterize the mechanisms and immunological effects of cat tolerance. It is a plan to further evaluate a unique, successful cohort of students at the University of Virginia who have experienced a marked decrease in exposure to cat allergen by moving from a home with a cat to university housing. The first phase of the study relates serial questionnaires, percutaneous testing with allergen extracts, and serum antibody levels. The second part utilizes repeated measurements of systemic allergic inflammation as well as upper and lower airway inflammation. The third aim focuses on T cell proliferative and functional responses to whole cat allergen and peptides during decreased exposure to cat allergen. This career development award will allow Dr. Erwin to answer an important clinical research question about changes in immune tolerance associated with decreased allergen exposure. Working with her experienced mentors and taking formal classes in epidemiology and biostatistics will provide her with the skills and foundation of knowledge necessary to complete these studies and impact the prevalence of allergic disease. Asthma is an increasingly common disease among children throughout the world but the cause is not understood. These studies will characterize immune responses that occur with natural changes in allergen exposure. The information gained will be used to decrease the prevalence of allergic disease in the future.